Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization

Li-xin WANG; Wen-bin WU; Zi-hang XU; Xiao-ning JIAO; Lin SU; Yang-zhuang-zhuang ZHU; Xiao CHEN; Chun-pu ZOU; Shi-guo ZHU

doi:10.13422/j.cnki.syfjx.20190822

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Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization

Research on Anti-lung Cancer Effect of TCM Compound and Its Effective Components | 更新时间：2021-02-09

- Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 14, Pages: 19-24(2019)
- 作者机构：
  
  上海中医药大学，上海　 201203
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190822
  CLC： R22; R242; R2-031; R285.5;R392.5; R273
- Published：20 July 2019，
  
  Published Online：04 January 2019，
  
  Received：08 October 2018，
- 稿件说明：
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Li-xin WANG, Wen-bin WU, Zi-hang XU, et al. Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):19-24(2019)
DOI：

Li-xin WANG, Wen-bin WU, Zi-hang XU, et al. Anti-tumor Effect of Astragaloside by Inducing M1 Macrophage Polarization. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):19-24(2019) DOI： 10.13422/j.cnki.syfjx.20190822.

摘要

目的：

探讨黄芪甲苷对巨噬细胞极化的影响及其可能的抗肿瘤免疫机制。

方法：

通过噻唑兰(methylthiazolyldiphenyl-tetrazolium bromide，MTT)比色法检测不同浓度黄芪甲苷作用不同时间，对巨噬细胞的细胞毒作用，以选取合适的黄芪甲苷作用浓度；将巨噬细胞与肿瘤细胞以1∶1进行共孵育，并用0.1 mg·L

－1

黄芪甲苷作用24 h，通过虫荧光素酶(luciferase，Luc)杀伤实验检测巨噬细胞对肿瘤细胞的杀伤效率；以0.1 mg·L

－1

黄芪甲苷作用巨噬细胞24 h，通过流式细胞术检测巨噬细胞CD16/32，CD206表达，通过实时荧光定量聚合酶链式反应(Real-time PCR)检测巨噬细胞诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)，精氨酸-1(Arginine-1，Arg-1)及细胞因子白细胞介素-1

(interleukin-1

，IL-1

)，肿瘤坏死因子-

(tumor necrosis factor-

，TNF-

)，白细胞介素-12(interleukin-12，IL-12)，白细胞介素-10(interleukin-10，IL-10)，转化生长因子-

(transforming growth factor-

，TGF-

)mRNA表达，通过蛋白免疫印迹法(Western blot)检测巨噬细胞信号传导及转录激活因子1(Signal transducers and activators of transcription 1

STAT1)，磷酸化信号传导及转录激活因子1(phosphorylation signal transducers and activators of transcription 1

p-STAT1)表达。

结果：

当黄芪甲苷质量浓度为0.1 mg·L

－1

时，对巨噬细胞无细胞毒作用。与空白组比较，Luc杀伤实验结果显示黄芪甲苷可以显著促进巨噬细胞介导的肿瘤杀伤；Real-time PCR结果显示黄芪甲苷可以诱导巨噬细胞表面M1型巨噬细胞标志CD16/32表达增高，促进M1型巨噬细胞特异性指标iNOS mRNA表达，同时诱导M1型巨噬细胞相关细胞因子IL-1

，TNF-

，IL-12 mRNA表达增高；Western blot结果显示黄芪甲苷可以促进巨噬细胞STAT1发生磷酸化。

结论：

黄芪甲苷可以通过促进巨噬细胞内STAT1发生磷酸化，进而诱导巨噬细胞向M1型巨噬细胞发生极化，并启动巨噬细胞相关的抗肿瘤免疫应答。

Abstract

Objective:

To investigate the effect of astragaloside on the macrophage polarization and the possible anti-tumor immunity mechanism of astragaloside.

Method:

The cytotoxic effect of different concentrations of astragaloside at different time points on macrophage was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT)

in order to choose the suitable concentration of astragaloside

macrophages were co-cultured with tumor cells at the ratio 1∶1

and the effect of astragaloside on macrophage-mediated lysis of tumor cells was performed by biophotonic cytotoxicity assay after the mixed cells were effected with 0.1 mg·L

-1

astragaloside for 24 h. Macrophages were dealt with 0.1 mg·L

-1

astragaloside for 24h

the expressions of CD16/32 and CD206 in macrophages were performed by flow cytometry

the mRNA expressions of macrophage inducible nitric oxide synthase (iNOS)

Arginine-1 (Arg-1)

interleukin-1

(IL-1

)

tumor necrosis factor-

(TNF-

)

interleukin-12 (IL-12)

interleukin-10 (IL-10) and transforming growth factor-

(TGF-

) were measured by Real-time PCR

the protein expressions of macrophage signal transducers and activators of transcription 1 (STAT1) and phosphorylation signal transducers and activators of transcription 1 (p-STAT1) were determined by Western blot.

Result:

Astragaloside had no effect on the viability of macrophages with 0.1 mg·L

-1

. Compared with control group

astragaloside obviously enhanced the macrophage-mediated lysis of tumor cells according to the biophotonic cytotoxicity assay

induced the M1 macrophage marker CD16/32 expression according to flow cytometry

increased the mRNA expressions of iNOS

IL-1

TNF-

and IL-12 according to the Real-time PCR

and promoted the phosphorylation of STAT1 in macrophages on the basis of Western blot.

Conclusion:

Astragaloside could induce M1 macrophage polarization by increasing the phosphorylation of STAT1

and initiate macrophage-related anti-tumor immunity response.

关键词

黄芪甲苷巨噬细胞肺癌免疫调节

Keywords

astragalosidemacrophagelung cancerimmunity regulation

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